The varicella-zoster virus (VZV) causes the most widespread childhood infection not yet amenable to vaccine control. It is associated with significant morbidity and mortality expecially among the immunosuppressed both during primary infection and during reactivation (shingles). Its control has been hampered by difficulties in virus propagation and purification related to its cell-associated nature in vitro. We propose to continue to search for a more efficient propagation system employing a variety of cell lines (both fibroblastic and epithelioid) and using the appearance of CPE, VZV particles as seen in the electron microscope, and hybridizable VZV mRNA and DNA as criteria for yield. VZV nucleocapsids will be purified to provide a source of viral DNA and to eliminate host proteins from the preparation. VZV DNA will also be purified directly from infected cells using the Hirt procedure. The site of varicella-zoster latency will be investigated by analyzing human dorsal ganglia DNA for the presence of VZV-specific nucleic acids. We will infect human neuronal cells in vitro to probe the mechanism of VZV latency. The question of VZV oncogenicity will be evaluated by continuing our in vitro transformation experiments. Varicella-zoster virus infection transforms hamster embryo cells. These cells demonstrate newly acquired VZV-specific surface antigens and Fc receptors. They produce tumors in syngeneic hamsters. We intend to quantitate the frequency of VZV-induced transformation and document the presence of VZV-specific nucleic acids in the transformed cells.